A Study of ABT-414 in Subjects With Solid Tumors

Study Overview
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Brief Summary
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A study of ABT-414 in subjects with solid tumors.

Official Title
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A Phase 1/2 Study Evaluating the Safety, Pharmacokinetics and Efficacy of ABT-414 in Subjects With Advanced Solid Tumors Likely to Over-Express the Epidermal Growth Factor Receptor (EGFR)

Conditions
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Squamous Cell Tumors

Intervention / Treatment
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* Drug: ABT-414


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have a solid tumor type likely to over-express Epidermal Growth Factor Receptor (EGFR) (Phase 1) Subjects have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 Subjects have available tumor tissue Subjects have adequate bone marrow, renal, and hepatic function as follows: Bone marrow: Absolute neutrophil count (ANC) >/= 1,500/mm3 Platelets >/= 100,000/mm3; Hemoglobin >/= 9.0 g/dL Renal function: Serum creatinine </= 1.5 times the upper limit of the institution's normal range Hepatic function: Bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) </= 1.5 times the upper limit of the institution's normal range. Subjects with liver metastasis may have an AST and ALT of </= 5.0 x the upper limit of normal. Subjects in the Phase 2 portion must have squamous cell Non-Small Cell Lung Cancer (NSCLC) Eligibility is restricted to subjects with confirmed EGFR amplification in the EGFR amplified cohort Exclusion Criteria: The subject has uncontrolled metastases to the central nervous system (CNS). Subjects with brain metastases are eligible provided they have shown clinical and radiographic stable disease for at least 28 days after definitive therapy and have not received prior whole brain radiation (Phase 1 only). The subject has received anticancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal, biologic, or any investigational therapy within a period of 28 days prior to the first dose of ABT-414. The subject has unresolved clinically significant toxicities from prior anticancer therapy, defined as any Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or higher. The subject had had major surgery within 28 days prior to the first dose of ABT-414. The subject has a history of immunologic reaction to any Immunoglobulin G (IgG) containing agent. Phase 2 portion only: The subject has previous or concurrent cancer that is distinct in primary site or histology from NSCLC, except cervical carcinoma in situ, non-melanoma carcinoma of the skin or in situ carcinoma of the bladder. Any cancer curatively treated greater than 3 years prior to entry is permitted.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABT-414<br>Subjects with solid tumors (Phase 1) and squamous non-small cell lung cancer (NSCLC) (Phase 2) | Drug: ABT-414<br>* ABT-414 will be administered by intravenous infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 - Safety (Number of subjects with adverse events and/or dose limiting toxicities) | Evaluation of vital signs, clinical lab testing, adverse event monitoring, physical exam and electrocardiogram (ECG) (periodic) under different dosing schedules, drug infusion times, and manufacturing processes. | Every 1-3 weeks for an average of 20 weeks | 
| Phase 1 - Pharmacokinetic profile | Cmax, Cmin, and half-life | Multiple timepoints Week 1 and Week 7 | 
| Phase 2 - Efficacy | Objective response per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST) | Every 6-9 weeks for an average of 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 2- Safety (Scheduled study visits occurring on average every 3 weeks) | Evaluation of vital signs, clinical lab testing, and adverse event monitoring, physical exam, and electrocardiogram (periodic) | Followed on average every 3 weeks for approximately 20 weeks | 
| Phase 2- Pharmacokinetic profile | Cmax, Cmin, and half-life | Multiple timepoints Week 1 | 
| Phase 1&2 - QT assessment | Triplicate electrocardiograms | Week 1 |