Study of Dalantercept 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.