A Phase 1 Study of the Safety and Pharmacokinetics of AGS-16M18 in Subjects With Advanced Renal Cell Cancer

Study Overview
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Brief Summary
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This is a first in human study of AGS-16M18 given every week to subjects with advanced renal cell cancer. AGS-16M18 will be administered as a 60 minute IV infusion on consecutive days until the disease worsens.

Detailed Description
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Subjects will be enrolled sequentially into 5 planned dose cohorts according to a standard, dose escalation study design. A disease assessment will be performed at study week 5 (+/- 3 days) by the investigator. The assessment will be based both on changes in clinical symptoms, and radiographic images. Subjects without evidence of disease progression may receive AGS-16M18 extended therapy at the dose and schedule of their assigned cohort until disease progression or intolerability of AGS-16M18. Disease assessments will be performed every 8 weeks during the extended period. A safety follow-up visit will occur 4 weeks after the last infusion of AGS-16M18.

Official Title
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A Phase 1, Open-Label, Multi-center, Dose Escalation Study of the Safety and Pharmacokinetics of AGS-16M18 Given as Monotherapy in Subjects With Advanced Renal Cell Carcinoma

Conditions
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Carcinoma, Renal Cell, Kidney Neoplasms, Kidney Diseases

Intervention / Treatment
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* Biological: AGS-16M18


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic or cytologic diagnosis (recent or remote) of metastatic renal cell carcinoma (including papillary, clear cell, and excluding transitional cell types) that is not amendable to cure by surgery or other means, and must have failed at least one prior systemic therapy, including but not limited to treatment with sunitinib, temsirolimus or sorafenib Evaluable/Measureable disease according to Response Criteria for Solid tumors Eastern Cooperative Group performance status of 0-1 Therapeutic anti-coagulation (PT, and/or INR, PTT) permitted, if clinically stable and >/= 3 months from initiation Exclusion Criteria: Past or present documented central nervous system (CNS) tumor or CNS metastasis Use of investigational drug (including marketed drugs not approved for this indication) within 4 weeks prior to screening or 5 half-lives of the prior investigational drug (whichever is longer) History of thromboembolic events and bleeding disorders </= 3 months (e.g., DVT or PE) Major Surgery (that requires general anesthesia) within 4 weeks of study enrollment

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: 1. AGS-16M18 Dose 1<br> | Biological: AGS-16M18<br>* IV Infusion<br>|
| Experimental: 2. AGS-16M18 Dose 2<br> | Biological: AGS-16M18<br>* IV Infusion<br>|
| Experimental: 3. AGS-16M18 Dose 3<br> | Biological: AGS-16M18<br>* IV Infusion<br>|
| Experimental: 4. AGS-16M18 Dose 4<br> | Biological: AGS-16M18<br>* IV Infusion<br>|
| Experimental: 5. AGS-16M18 Dose 5<br> | Biological: AGS-16M18<br>* 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 |  | Throughout the treatment | 
| Assessment of PK variables |  | Weeks 0 - 5, week 8, weekly during extension period, 2 and 3 months after last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of anti-AGS-16M18 antibody formation |  | Week 0, week 1, week 4, week 8, every 8 weeks during extension period, 2 and 3 months after last dose | 
| Changes in tumor status |  | Week 5, week 8, every 8 weeks during extension period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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clinical trial, phase 1, carcinoma, advanced renal cell, kidney, pharmacokinetics, safety, AGS-16M18