A Phase 2 Randomized Study of Dalantercept in Combination With Axitinib Compared to Axitinib Alone in Patients With Advanced Renal Cell Carcinoma

Key

Inclusion Criteria:

- Histologically confirmed, advanced, predominantly clear cell renal cell carcinoma
(RCC).

- Part 1: Progression of disease following up to three lines of prior therapy,
including at least one approved VEGF receptor tyrosine kinase inhibitor for RCC.
Adjuvant therapy is permitted as one line of prior therapy.

- Part 2: Progression of disease following one first-line regimen of a VEGF receptor
tyrosine kinase inhibitor (either sunitinib or pazopanib). Patients with disease
recurrence after completion of adjuvant therapy with either sunitinib or pazopanib
who also received treatment with either agent in the advanced setting are eligible.

- A minimum of 2 weeks since the last dose of prior therapy (a minimum of 4 weeks since
bevacizumab +/- interferon).

- Measurable disease that is evaluable by Response Evaluation Criteria in Solid Tumors
(RECIST) v1.1.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

- Life expectancy of at least 12 weeks.

- Clinical laboratory values within acceptable ranges within 72 hours prior to study
day 1.

Key Exclusion Criteria:

- Clinically significant organ/system disease unrelated to RCC that in the judgment of
the investigator should preclude treatment with dalantercept or axitinib.

- Clinically significant cardiovascular risk.

- Known central nervous system (CNS) metastases or leptomeningeal disease. Patients
with CNS metastases treated with whole brain radiotherapy, gamma knife, and/or
surgery who are considered stable by CNS imaging and are not being treated with
corticosteroids within 6 weeks prior to study day 1 may be enrolled.

- Active gastrointestinal (GI) bleeding, unrelated to RCC.

- Any active malignancy, other than RCC, for which chemotherapy or other anti-cancer
therapy is indicated. Patients with adequately treated non-melanoma skin cancer, in
situ cancer, or other cancer from which the subject has been disease-free for at
least 5 years will be permitted.

- Any lesion invading or having encasement ≥ 180 degrees around the wall of a major
blood vessel as assessed by computed tomography (CT) scan and/or magnetic resonance
imaging (MRI).

- Radiotherapy within 2 weeks prior to study day 1.

- Lack of recovery from toxic effects of previous chemotherapy, radiation therapy,
biologic therapy, and/or experimental therapy to ≤ grade 1 with the exception of
alopecia.

- Patients undergoing renal dialysis.

- Major surgery within 4 weeks prior to study day 1 (patients must have recovered
completely from any previous surgery prior to study day 1).

- Any active infection requiring parenteral antibiotic therapy within 1 month prior to
study day 1 or systemic antibiotics within 2 weeks of study day 1.

- Anti-coagulation therapy (e.g., clopidogrel, dabigatran, warfarin, and heparin).

- Current use of drugs or substances that interact with cytochrome P450 enzymes.

- Peripheral edema ≥ grade 2 within 2 weeks prior to study day 1.

- BMI < 16 kg/m2

- Clinically significant active pulmonary risk including pulmonary hypertension and
pulmonary edema within 12 months of study day 1 or pulmonary embolism within 6 months
of study day 1.

- Bleeding diathesis including clinically significant platelet disorders, epistaxis,
active hemoptysis (defined as bright red blood of ≥ 1/2 teaspoon [2.5 mL] in any 24
hour period) within 2 weeks prior to study day 1; no risk of further bleeding must be
clearly documented.

- History of hereditary hemorrhagic telangiectasia (HHT).

- Any prior treatment with dalantercept or any other agent targeting ALK1 pathway.

- Any prior treatment with axitinib.

- Pregnant or lactating female patients.