Study of ABT-700 in Subjects With Advanced Solid Tumors

Safety (Number of subjects with adverse events and/or dose-limiting toxicities) [ Time Frame: Assessments will be made at three time points during the first 21 day cycle, once per cycle thereafter up to one year or until therapy is deemed unsatisfactory as evidenced by clinically significant progression of disease, plus 30 days after last dose. ] [ Designated as safety issue: Yes ]
- Evaluation of vital signs, clinical lab testing, physical exams and adverse event monitoring
Pharmacokinetics of ABT-700 when administered as monotherapy and in combination with erlotinib or with XELOX including maximum observed plasma concentration (Cmax) and other variables. [ Time Frame: Samples will be taken at three time points during the first 21 day cycle, once per cycle thereafter up to one year or until therapy is deemed unsatisfactory as evidenced by clinically significant progression of disease, plus 30 days after last dose. ] [ Designated as safety issue: Yes ]
- Blood samples for assay of ABT-700

QT Assessment [ Time Frame: Assessments will be made several times during the first four administrations, plus 30 days after last dose. ] [ Designated as safety issue: Yes ]
- Triplicate ECGs
Pharmacodynamics of ABT-700 when administered as monotherapy and in combination with erlotinib or with XELOX to define the relationship between drug concentration and disease status. [ Time Frame: Samples will be taken at three time points during the first 21 day cycle, once per cycle thereafter up to one year or until therapy is deemed unsatisfactory as evidenced by clinically significant progression of disease, plus 30 days after last dose. ] [ Designated as safety issue: No ]
- Pharmacodynamics of ABT-700 analyzed from blood samples.

Eligibility Criteria

Inclusion Criteria

Subject with advanced solid tumors.
Subject must have disease:
1. that is not amenable to surgical resection, or
2. that has progressed or recurred despite standard therapy, or
3. that has failed to respond to standard therapy, or
4. for which no effective therapy exists. • Subject cannot tolerate or must not be eligible for other approved therapeutic options with known survival advantage.
Subjects enrolled on the combination therapy phase must satisfy the above inclusion criteria and also the following:
- Combination therapy Cohort A subjects must have non small cell lung cancer (NSCLC) that has progressed after one or more prior therapies and be eligible to receive erlotinib in combination with ABT-700.
- Combination therapy Cohort B subjects must have inoperable, locally advanced or metastatic Human Epidermal Growth Factor Receptor 2 (HER2)
- negative gastric / gastroesophageal junction adenocarcinoma with no prior therapy for metastatic disease and be eligible to receive oxaliplatin and capecitabine (XELOX) in combination with ABT-700.

Exclusion Criteria

Subject has received anticancer therapy including chemotherapy, immunotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within a period of 21 days, or herbal therapy within 7 days prior to the first dose of ABT-700.
- Palliative radiation therapy for painful bony or skin metastasis for 10 fractions or less is not subject to a washout period.
Subjects with uncontrolled metastases of the central nervous system. Subjects with brain metastases are eligible provided they have shown clinical and radiographic stable disease and have not used steroids for at least 1 month after definitive therapy.
Subjects enrolled on the combination therapy phase must satisfy the above exclusion criteria and also the following:
- Combination therapy Cohort A, subjects with NSCLC, who are ineligible for erlotinib will be excluded.
- Combination therapy Cohort B, subjects with inoperable, locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma, who are ineligible to receive XELOX chemotherapy, who are HER2+, or who have received prior chemotherapy for metastatic disease will be excluded (adjuvant treatment with chemotherapy/radiation therapy ≥ 6 months from Cycle 1 Day 1 is allowed).