Study of MDX-1203 in Subjects With Advanced/Recurrent Clear Cell Renal Cell Carcinoma (ccRCC) or Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma (B-NHL)

Study Overview
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Brief Summary
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The purpose of this study is to determine if MDX-1203 is safe for the treatment of renal cell carcinoma or non-hodgkin's lymphoma.

Detailed Description
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Multicenter, open-label, dose-escalation, multidose study of MDX-1203, a fully human monoclonal antibody drug conjugate targeting the CD70 transmembrane cell-surface protein which is highly expressed in ccRCC and B-NHL. MDX-1203 is composed of a human anti-CD70 monoclonal antibody covalently linked to a prodrug form of a cytotoxic deoxyribonucleic acid (DNA) minor-groove binding agent (MGBA). The study will consist of 3 periods: Screening (up to 28 days), Treatment (up to 17 cycles or 2 years), and Follow-up (up to 6 months).

Official Title
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A Phase I, Multicenter, Open-Label, Dose-Escalation, Multidose Study of MDX-1203 in Subjects With Advanced/Recurrent Clear Cell Renal Cell Carcinoma or Relapsed/Refractory B-Cell Non Hodgkin's Lymphoma

Conditions
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Renal Cell Carcinoma, Non-hodgkin's Lymphoma

Intervention / Treatment
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* Biological: MDX-1203


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 Criteria specific to each tumor type: For Clear cell renal cell carcinoma (ccRCC): advanced or recurrent disease. Must have failed at least 1 prior systemic therapy For B-cell non-Hodgkin's lymphoma (B-NHL): Must have failed at least 1 prior systemic therapy Measurable disease criteria by tumor type: For ccRCC: At least 1 unidimensional measurable lesion For B-NHL: At least 1 bidimensionally measurable lesion Prior therapies for advanced/recurrent ccRCC or relapsed/refractory B-NHL or have become intolerant to a systemic therapy Provide archived or fresh tumor tissue for CD70 status. Subjects must be CD70+ Provision of fresh tissue (pre-treatment and on-treatment) for exploratory analysis is mandatory for at least 5 and a maximum of 10 B-NHL subjects Exclusion Criteria: Prior therapy with an anti-CD70 antibody History of severe hypersensitivity reactions to other monoclonal antibodies Active or untreated central nervous system lymphoma Active infection (viral, bacterial, or fungal) Evidence of bleeding diathesis or coagulopathy Active autoimmune disease requiring immunosuppressive therapy Known current drug or alcohol abuse

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: MDX-1203<br>Accelerated titration design (ATD)of 6 dose levels. Subjects will be assigned to a dose level in the order they enter the study | Biological: MDX-1203<br>* Assigned Interventions: Single dose of MDX-1203 will be administered every 21 days as an intravenous (i.v.) infusion. Subjects will receive one dose of MDX-1203.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety profile of MDX-1203 and determine the maximum tolerated dose (MTD) |  | up to 17 cycles | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarker: Incidence of CD70+ tumors in target population |  | Screening |