A Trial of PT2977 in Combination With Cabozantinib in Patients With Clear Cell Renal Cell Carcinoma (ccRCC)

This is an open-label Phase 2 study which will evaluate the efficacy and safety of PT2977 in
combination with cabozantinib in patients with advanced ccRCC. PT2977 will be administered
orally and cabozantinib will be administered orally once daily.

Inclusion Criteria:

- Has the ability to understand and willingness to sign a written informed consent form
before the performance of any study-specific procedures

- 18 years of age or older

- Has locally advanced or metastatic RCC with predominantly clear cell subtype

- Has at least one measurable lesion as defined by RECIST version 1.1

- Eastern Cooperative Oncology Group (ECOG) 0-1

- Has adequate organ function defined as follows:

- Absolute neutrophil count ≥ 1,000/µL, hemoglobin level ≥ 10 g/dL and platelet
count ≥ 100,000/µL without transfusion or growth factor support within 2 weeks
prior to obtaining the hematology values at screening;

- Serum creatinine level ≤ 2.0 × upper limit of normal (ULN)

- Transaminase levels (AST/ALT) ≤ 3.0 × upper limit of normal (ULN); total
bilirubin (TBILI) ≤ 1.5 mg/dL in the absence of Gilbert's disease

- Cohort 1: Patients must not have received prior systemic therapy for advanced or
metastatic ccRCC

- Cohort 2: Patients must have received prior immunotherapy and no more than two prior
treatments for advanced or metastatic ccRCC

Exclusion Criteria:

- Has received prior treatment with PT2977 or other HIF2α inhibitors

- Has received prior treatment with cabozantinib

- Has had radiation therapy for bone metastases within two weeks of starting study drug

- Has a history of untreated brain metastases 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 anticoagulant therapy

- 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 3 months before first study drug administration

- Has an active infection requiring systemic treatment

- Is participating in another therapeutic clinical trial