A Trial of PT2977 Tablets In Patients With Advanced Solid Tumors

Part 1A: This is a Phase 1, multiple-dose, dose-escalation trial of PT2977 Tablets, where
patients with advanced solid tumors will be assigned to sequential dose cohorts. Patient
safety will be monitored with frequent physical examinations, vital sign measurements,
electrocardiograms (ECGs), and hematology and chemistry laboratory studies, and by recording
all adverse events (AEs). Blood will be obtained for analysis of the concentration of PT2977
and to assess biomarkers.

Part 1B: Once the MTD and/or the RP2D is achieved, and expansion cohort of 25 patients with
advanced clear cell renal cell carcinoma (ccRCC) will be enrolled.

Part 2: After determination of the MTD/RP2D, up to 25 patients with other specified solid
tumors may be enrolled. Up to 3 different tumor types may be included in this part of the
study.

Part 2A: A cohort of 25 patients with glioblastoma (GBM)

Inclusion Criteria:

- Has a diagnosis of locally advanced or metastatic solid tumor

- Is of age ≥ 18 years

- Has a life expectancy of ≥ 6 months

- Has adequate organ function

- If a female patient, must be surgically sterile, post-menopausal, or must agree to use
physician-approved method of birth control during the study and for a minimum of 30
days after the last study drug administration, or if a male patient with a female
partner, must agree to use physician-approved method of birth control during the study
and for a minimum of 30 days after the last study drug administration

- Able to swallow oral medications

Additional Inclusion Criteria for GBM cohort

- Must have histologically confirmed glioblastoma, IDH-wild type that is first recurrent
following radiation therapy and temozolomide according to the Response Assessment in
Neuro-Oncology (RANO) criteria

- Must have archival tumor tissue available from a previous surgery for glioblastoma

- Must have measurable (defined as at least 1 cm x 1 cm) contrast-enhancing lesion by
MRI imaging within 21 days of starting treatment

- Must be able to undergo MRI of the brain with gadolinium. Patients must be maintained
on a stable or decreasing dose of corticosteroid regimen (no increase for 5 days)
prior to this baseline MRI

Exclusion Criteria:

- Has a history of untreated brain metastasis or history of leptomeningeal disease or
spinal cord compression

- Has failed to recover from the reversible effects of prior anticancer therapy

- Has uncontrolled or poorly controlled hypertension

- Has malabsorption due to prior gastrointestinal (GI) surgery or GI disease

- Has had any major cardiovascular event within 6 months prior to study drug
administration

- Has any other clinically significant cardiac, respiratory, or other medical or
psychiatric condition that might interfere with participation in the trial or
interfere with the interpretation of trial results

- Has had major surgery within 4 weeks before first study drug administration

- Has known HIV

- Has an active infection requiring systemic treatment

- Is participating in another therapeutic clinical trial

Additional Excusion Criteria for GBM cohort:

- Has received prior anti-VEGF therapy including bevacizumab (i.e. patients must be
bevacizumab naïve)

- Is receiving enzyme-inducing anti-epileptic drugs (EIAED). Patients may be on
non-enzyme inducing anti-epileptic drugs or not be taking any anti-epileptic drugs.
Patients previously treated with EIAED may be enrolled if they have been off the EIAED
for 10 days or more prior to the first dose of PT2977