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

Sponsor

Agensys, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01672775

Collaborator

(none)

Enrollment

Locations

Arms

55.2

Actual Duration (Months)

3.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Renal Cell Renal Cell Carcinoma of Papillary Histology Renal Cell Carcinoma With Clear Cell Histology Renal Cell Carcinoma With Non-Clear Cell Histology	Drug: AGS-16C3F	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

34 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 18, 2012

Actual Primary Completion Date :

Feb 21, 2017

Actual Study Completion Date :

Feb 21, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Incidence of Adverse Events [24 months]

Secondary Outcome Measures

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 [Days 1, 2, 3, 4, 8, 15, 22, 43, 64, 65, 66, 67, 71, 78, and 92]
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)
Incidence of antidrug antibody formation to human native antibody (AGS-16C) and antibody drug conjugate (AGS-16C3F) [24 months]
Tumor response: objective response rate [24 months]
Determined from the subjects' best response and will include complete response (CR) and partial response (PR)
Tumor response: disease control rate [24 months]
Determined from the subjects' best response will include complete response (CR) partial response (PR), and stable disease (SD)
Tumor response: Changes in bone scans [Baseline, Week 13 and every 12 weeks thereafter]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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