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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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

Conditions
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Carcinoma, Renal Cell, Renal Cell Carcinoma of Papillary Histology, Renal Cell Carcinoma With Clear Cell Histology, Renal Cell Carcinoma With Non-Clear Cell Histology

Intervention / Treatment
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* Drug: AGS-16C3F


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 AGS-16C3F highest dose<br>Renal Cell Carcinoma subjects with clear and non-clear histology | Drug: AGS-16C3F<br>* intravenous (IV) infusion<br>|
| Experimental: Cohort 0 AGS-16C3F higher dose<br>Renal Cell Carcinoma subjects with clear and non-clear histology | Drug: AGS-16C3F<br>* intravenous (IV) infusion<br>|
| Experimental: Cohort (-1) AGS-16C3F high dose<br>Renal Cell Carcinoma subjects with clear and non-clear histology | Drug: AGS-16C3F<br>* intravenous (IV) infusion<br>|
| Experimental: Cohort (-2) AGS-16C3F middle dose<br>Renal Cell Carcinoma subjects with clear and non-clear histology | Drug: AGS-16C3F<br>* intravenous (IV) infusion<br>|
| Experimental: Cohort (-3) AGS-16C3F low dose<br>Renal Cell Carcinoma subjects with clear and non-clear histology | Drug: AGS-16C3F<br>* intravenous (IV) infusion<br>|
| Experimental: Cohort (-4) AGS-16C3F lowest dose<br>Renal Cell Carcinoma subjects with clear and non-clear histology | Drug: AGS-16C3F<br>* intravenous (IV) infusion<br>|
| Experimental: AGS-16C3F in RCC Subjects with Clear Cell Histology<br>Expansion Cohort | Drug: AGS-16C3F<br>* intravenous (IV) infusion<br>|
| Experimental: AGS-16C3F in RCC Subjects with Papillary Histology<br>Expansion Cohort | Drug: AGS-16C3F<br>* intravenous (IV) infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile for total antibody (TAb), antibody drug conjugate (ADC), and monomethyl auristatin F (MMAF): Ceoi or Cmax, Ctrough, Tmax, AUCτ, t1/2, CL, and Vss | Concentration at end of infusion (Ceoi) or maximum observed concentrations (Cmax), Trough concentration (Ctrough), time to maximum concentration (Tmax), partial area under the serum concentration-time curve (AUCτ), terminal or apparent half-life (t1/2), systemic clearance (CL), and volume of distribution at steady state (Vss) | Days 1, 2, 3, 4, 8, 15, 22, 43, 64, 65, 66, 67, 71, 78, and 92 | 
| Incidence of antidrug antibody formation to human native antibody (AGS-16C) and antibody drug conjugate (AGS-16C3F) |  | 24 months | 
| Tumor response: objective response rate | Determined from the subjects' best response and will include complete response (CR) and partial response (PR) | 24 months | 
| Tumor response: disease control rate | Determined from the subjects' best response will include complete response (CR) partial response (PR), and stable disease (SD) | 24 months | 
| Tumor response: Changes in bone scans |  | Baseline, Week 13 and every 12 weeks thereafter | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal Cell Carcinoma, AGS-16C3F, Pharmacokinetics of AGS-16C3F