3.0 PATIENT SELECTION

For questions regarding eligibility criteria, see the Study Resources page. Please note that the Study Chair cannot grant waivers to eligibility requirements.

3.1 On-Study Guidelines

This clinical trial can fulfill its objectives only if patients appropriate for this trial are enrolled. All relevant medical and other considerations should be taken into account when deciding whether this protocol is appropriate for a particular patient: for example, medical conditions such as uncontrolled infection, uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient. Clinicians should use their clinical judgement and have discussions with potential trial participants to assess their ability to follow protocol requirements safely.

Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom).

3.2 Eligibility Criteria (Step 1)

When calculating days of tests and measurements, the day a test or measurement is done is considered Day 0. Therefore, if a test were done on a Monday, the Monday one week later would be considered Day 7.

A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e. has had menses at any time in the preceding 12 consecutive months).

3.2.1 Documentation of Disease

Histologic Documentation: Histologically-proven glioblastoma (WHO 2021 criteria)

Stage: Progressive or recurrent disease per RANO criteria

No IDH mutation (IDH1 R132H negative by IHC or sequencing)

3.2.2 Prior Treatment

Patients must be in first recurrence of glioblastoma following radiation therapy and temozolomide.

No prior therapies except radiation, surgery, temozolomide, TTFields, and/or Gliadel

wafers (placed during the first surgery at diagnosis of GBM). Prior radiation therapy,

TTFields, or placement of Gliadel wafers must be completed at least 2 weeks prior to

registration. Prior temozolomide must be completed at least 3 weeks prior to

registration.

No prior use of nivolumab or other anti-PD1 agents.

Patients must be neurologically stable off corticosteroids for at least 5 days prior to registration.

3.2.3 Age: 18 years or older

3.2.4 Karnofsky Performance Status: ≥ 60% (i.e. patient must be able to care for themselves with occasional help from others)

3.2.5 Required Initial Laboratory Values:

Absolute Lymphocyte Count (ALC): ≥ 1000/mm3

Absolute Neutrophil Count (ANC): ≥ 1500/mm3

Platelet Count: ≥ 100,000/mm3

Hemoglobin: ≥ 9.0 g/dL

APTT or PTT: ≤ 1.5 x upper limit of normal (ULN)

Total Bilirubin: < 2.0 x ULN*

AST / ALT: < 3.0 x ULN

Calc. Creatinine Clearance (CrCl): ≥ 50 mL/min**

• Except for patients with Gilbert’s syndrome, who must have direct bilirubin < 2.0 x ULN

** Calculated by Cockcroft-Gault equation.

3.2.6 Not pregnant and not nursing, because this study involves an investigational agent

whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn

are unknown and an agent that has known genotoxic, mutagenic and teratogenic effects.

Therefore, for women of childbearing potential only, a negative pregnancy test done within

14 days prior to registration is required.

Comorbid Conditions

3.2.7 Patients with a prior or concurrent malignancy whose natural history or treatment does