A Study of RO5458640 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This multicenter, open-label, multiple ascending dose study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of RO5458640 in patients with advanced solid tumors. Cohorts of patients will receive ascending doses of RO5458640 intravenously, either weekly or every 2 weeks or every 3 weeks, until disease progression or unacceptable toxicity occurs.

Official Title
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A Phase I Multiple Ascending Dose (MAD) Study of RO5458640, a Humanized Monoclonal Antibody Against the TNF-like Weak Inducer of Apoptosis (TWEAK) Ligand, in Patients With Advanced Solid Tumors

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: RO5458640


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, >/= 18 years of age Histologically or cytologically confirmed malignant solid tumors Measurable and/or evaluable disease according to RECIST 1.1 criteria Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Adequate bone marrow, liver and renal function Exclusion Criteria: Prior chemotherapy, radiotherapy, or hormonal therapy for cancer within 3 weeks of first study treatment, except for short course palliative radiotherapy for pain Antibody therapy or other immunotherapy currently or less than 21 days prior to study treatment Current immunosuppressive therapy, including those prescribed for organ transplantation and rheumatologic disease Corticoid therapy > 10 mg/day prednisone or equivalent Patients who have not recovered from > grade 1 (NCI CTCAE) prior adverse events from any cancer therapy, except for alopecia Pregnant or breastfeeding women Known hypersensitivity to any component of RO5458640 or previous severe hypersensitivity reactions to monoclonal antibody therapy History of active seizure disorder History of CNS or leptomeningeal metastases, except for clinically stable disease for at least 3 weeks prior to first study drug Cardiovascular illness: CVA or MI < 6 months prior to study, CHF > NYHA Class 2, QTcF >480 msec. Active infection

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: Single Arm<br> | Drug: RO5458640<br>* Multiple ascending doses intravenously, weekly or every 2 weeks or every 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Incidence of adverse events |  | approximately 2 years | 
| Dose Limiting Toxicity (DLT) according to CTEP Common Terminology Criteria for Adverse Events Version 4.0 |  | approximately 2 years | 
| Maximum Tolerated Dose (MTD) |  | approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: area under the concentration - time curve (AUC) on two administration schedules |  | approximately 2 years | 
| Tumor response according to RECIST criteria |  | approximately 2 years | 
| Antigenicity: Human anti-human antibody [HAHA] profile |  | approximately 2 years |