A Phase 1, Dose-Escalation Trial of PT2385 Tablets In Patients With Advanced Clear Cell Renal Cell Carcinoma

PART 1: This is a Phase 1, multiple-dose, dose-escalation trial of PT2385 Tablets, where
patients with advanced ccRCC 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 PT2385 and to assess
biomarkers.

PART 2: This is a Phase 1 trial of PT2385 Tablets in combination with nivolumab, where
patients with advanced ccRCC will be assigned to dose cohorts. Patient safety will be
monitored with frequent physical examinations, vital sign measurements, ECGs, and hematology
and chemistry laboratory studies, and by recording all AEs. Blood will be obtained for
analysis of the concentration of PT2385 and to assess biomarkers.

PART 3: This is a Phase 1 trial of PT2385 Tablets in combination with cabozantinib tablets,
where patients with advanced ccRCC will be assigned to dose cohorts. Patient safety will be
monitored with frequent physical examinations, vital sign measurements, ECGs, and hematology
and chemistry laboratory studies, and by recording all AEs. Blood will be obtained for
analysis of the concentration of PT2385 and cabozantinb and to assess biomarkers.

Inclusion Criteria

PART 1

- Has locally advanced or metastatic ccRCC and has progressed during treatment with at
least one prior therapeutic regimen

- Is of age ≥ 18 years

- Has a life expectancy of ≥ 3 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

PART 2 - In addition to PART 1

- Received no more than three prior systemic treatment regimens in the advanced or
metastatic setting

- Must have received at least one but not more than two prior anti-angiogenic therapy
regimens

PART 3 - In addition to PART 1

• Must have received at least one vascular endothelial growth factor receptor (VEGFR)
targeting tyrosine kinase inhibitor

Exclusion Criteria

PART 1

- 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

- Is receiving warfarin anticoagulant therapy or expected to require warfarin

- 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

PART 2 - In addition to PART 1

- Has received prior immunotherapy

- Has any active or recent history of a known or suspected autoimmune disease

PART 3 - In addition to PART 1

- Gastrointestinal (GI) disorders

- Any history of congenital long QT syndrome