A Study to Assess the Safety, Pharmacokinetics and Effectiveness of AGS-16C3F Monotherapy in Subjects With Renal Cell Carcinoma (RCC) of Clear Cell or Papillary Histology

A Phase 1, Open Label, Multi-center Study to Assess the Safety, Pharmacokinetics and Effectiveness of AGS-16C3F Monotherapy in Subjects With Renal Cell Carcinoma (RCC) of Clear Cell or Papillary Histology

The purpose of this study is to evaluate the safety and pharmacokinetics and assess the immunogenicity and effectiveness of AGS-16C3F in subjects with renal cell cancer (RCC).

The study has two components. The first aims to establish a safe dose for AGS-16C3F. Once identified, the safety and effectiveness will be tested in additional subjects with either clear cell or papillary histology in expanded cohorts.

Inclusion Criteria:

• Dose determination cohorts: Histologically confirmed diagnosis of metastatic RCC of either clear cell or non-clear histology.

  • Tumors with clear cell histology: subject must have progressed after at least one anti-vascular endothelial growth factor receptor (anti-VEGFR) therapy
  • Tumors with non-clear cell histology must be ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (ENPP3) positive at pre-screening. This sub-group does not have any prior therapy requirement.

• Dose expansion cohorts: Histologically confirmed diagnosis of metastatic RCC of either clear cell or papillary histology

  • Tumors with clear cell histology: subject must have progressed after at least one anti-VEGFR therapy
  • Tumors with papillary histology: includes unclassified histology with papillary features and must be ENPP3 positive at pre-screening. This sub-group does not have any prior therapy requirement.

• Measurable disease according to Response Criteria for Solid Tumors (RECIST Version 1.1)

• Eastern Cooperative Group (ECOG) performance status of 0-1

• Hematologic function, as follows:

  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
  • Platelet count ≥ 100 x 109/L
  • Hemoglobin ≥ 9 g/dL (transfusions are allowed)

• Renal function, as follows:

  • creatinine ≤ 1.5 x upper limit of normal (ULN), or calculated glomerular filtration rate (GFR) > 50 mL/min if creatinine > 1.5x ULN

• Hepatic function, as follows:

  • Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 x ULN or ≤ 5x ULN if known liver metastases
  • Total bilirubin ≤1.5 x ULN

• International normalized ratio (INR) < 1.3 (or ≤ 3.0 if on therapeutic anticoagulation)

• Women and men of childbearing potential must be advised and agree to practice effective methods of contraception during the course of the study and for 4 weeks after the last AGS-16C3F infusion administration

Exclusion Criteria:

• Current uncontrolled central nervous system (CNS) metastasis or malignant brain tumors
• Use of any investigational drug (including marketed drugs not approved for this indication) within 4 weeks prior to screening. No time limit applies to the use of marketed drugs approved for this indication provided that the subject has progressed on the treatment and all toxicities attributable to the drug have resolved or returned to baseline
• Known sensitivity to any of the ingredients of the investigational product AGS-16C3F
• History of thromboembolic events and bleeding disorders ≤3 months (e.g., (deep vein thrombosis) DVT or pulmonary embolism (PE))
• Active angina or Class III or IV Congestive Heart Failure (CHF) (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 12 months of study enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, congestive heart failure, uncontrolled hypertension, or arrhythmias not controlled by outpatient medication.
• Major surgery within 4 weeks of study enrollment
• Women who are pregnant (confirmed by positive pregnancy test) or lactating
• Known positive test for human immunodeficiency virus (HIV), hepatitis C, or hepatitis B surface antigen.
• Active infection requiring treatment with systemic (intravenous or oral) anti-infectives (antibiotic, antifungal, or antiviral agent) within 72 hours of screening.
• History of eye surgery within 6 months, presence of cataracts or other ocular disorders significantly affecting vision