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).

Study Overview

• Status: Completed
• Conditions: 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: Drug: AGS-16C3F

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Site CA00006 Cross Cancer Institute
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Site CA00008 British Columbia Cancer Agency
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • Site CA00009 London Health Sciences Centre
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Site CA00007 Jewish General Hospital
• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Site US00005 University of Michigan Medical Center
    • Detroit, Michigan, United States, 48201
      • Site US00003 Karmanos Cancer Institute
  • New York
    • Buffalo, New York, United States, 14263
      • Site US00004 Roswell Park Cancer Institute
    • New York, New York, United States, 10065
      • Site US00002 Memorial Sloan-Kettering Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Site US00001 Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

8

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Agensys, Inc.

Publications and helpful links

Helpful Links

• Link to results on the Astellas Clinical Study Results website.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 18, 2012
• Primary Completion (ACTUAL): February 21, 2017
• Study Completion (ACTUAL): February 21, 2017

Study Registration Dates

• First Submitted: August 22, 2012
• First Submitted That Met QC Criteria: August 22, 2012
• First Posted (ESTIMATE): August 27, 2012

Study Record Updates

• Last Update Posted (ACTUAL): December 19, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Renal Cell Carcinoma; AGS-16C3F; Pharmacokinetics of AGS-16C3F
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma
• Other Study ID Numbers: AGS-16C3F-12-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."