A Phase 1/2 Study of the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-Tumor Activity of the Oral ALK/EGFR Inhibitor AP26113

Inclusion Criteria

Patients must meet all the criteria for the cohort for which their entry is proposed.

PART 1: Dose Escalation Phase:

1. Histologically confirmed advanced malignancies. All histologies except leukemia

2. Refractory to available therapies or for whom no standard or available curative
treatments exist

3. Tumor tissue available for analysis.

PART 2: Expansion cohorts (4 additional cohorts):

1. Expansion cohort 1: Non-small cell lung cancer (NSCLC) patients whose tumors exhibit
anaplastic lymphoma kinase (ALK) rearrangements and who have not been treated with
previous ALK inhibitors.

- Histologically confirmed NSCLC

- Tumor tissue available for analysis

- ALK rearrangement by fluorescence in situ hybridization (FISH)

- No prior ALK inhibitor therapy.

2. Expansion cohort 2: NSCLC patients whose tumors exhibit ALK rearrangements and who
are resistant to crizotinib:

- Histologically confirmed NSCLC

- Tumor tissue available for analysis

- ALK rearrangement by FISH

- Resistant to crizotinib.

3. Expansion cohort 3: NSCLC patients whose tumors exhibit epidermal growth factor
receptor (EGFR) activating mutations and who are resistant to at least one (1) prior
EGFR inhibitor:

- Histologically confirmed NSCLC

- Tumor tissue available for analysis;

- Activating mutation in EGFR including point mutation or activating deletion;

- Resistant to at least one (1) prior EGFR inhibitor.

4. Expansion cohort 4: Patients with any cancers with abnormalities in ALK or other
targets against which AP26113 is active. Examples include, but are not limited to,
anaplastic large cell lymphoma (ALCL), diffuse large-cell lymphoma (DLCL),
inflammatory myofibroblastic tumors (IMT), and other cancers with ALK abnormalities,
or tumors with ROS fusions:

- Histologically confirmed lymphomas and other cancers except for leukemias

- Tumor tissue available for analysis.

General Eligibility Criteria:

All patients (irrespective of whether they are enrolled in PART 1 or PART 2) must meet
all the following eligibility criteria for study entry.

- All patients must have tumor tissue available for analysis. If sufficient tissue is
not available, patients must undergo a biopsy to obtain adequate samples.

- In the expansion cohorts, for which failure of prior therapy is specified (expansion
cohorts 2 and 3), tumor tissue must be obtained following failure to prior therapy.

- Must have measurable disease by Response Evaluation Criteria in Solid Tumors
(RECIST).

- Male or female patients ≥ 18 years old.

- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

- Minimum life expectancy of 3 months or more.

- Adequate renal and hepatic function.

- Adequate bone marrow function.

- Normal QT interval on screening electrocardiogram (ECG) evaluation.

- For females of childbearing potential, a negative pregnancy test must be documented
prior to enrollment.

- Female and male patients who are of childbearing potential must agree to use an
effective form of contraception with their sexual partners throughout study
participation.

- Signed and dated informed consent indicating that the patient has been informed of
all pertinent aspects of the study.

- Willingness and ability to comply with scheduled visits and study procedures.

Main Exclusion Criteria:

- Received an investigational agent within 14 days prior to initiating AP26113.

- Received systemic anticancer therapy or radiation therapy within 14 days prior to
initiating AP26113. (Except for FDA-approved TKIs targeted against EGFR or ALK, which
are allowed up to 72 hours prior to initiating AP26113 if the patient is free of
treatment-related toxicity)

- Received any prior agents targeted against ALK, with the exception of crizotinib.

- Major surgery within 28 days prior to initiating AP26113.

- Central nervous system metastases that are symptomatic or require steroid or
anticonvulsant use (unless discussed with and otherwise agreed to by the sponsor).

- Significant uncontrolled or active cardiovascular disease.

- Uncontrolled hypertension (diastolic blood pressure [BP] > 100 mm Hg; systolic > 150
mm Hg).

- Prolonged QT interval, or being treated with medications known to cause Torsades de
Pointes.

- History or presence of pulmonary interstitial disease.

- Ongoing or active infection. The requirement for intravenous (IV) antibiotics is
considered active infection.

- Known history of human immunodeficiency virus (HIV). Testing is not required in the
absence of history.

- Pregnant or breastfeeding.

- Malabsorption syndrome or other gastrointestinal illness that could affect oral
absorption of AP26113.

- Any condition or illness that, in the opinion of the Investigator, would compromise
patient safety or interfere with the evaluation of the safety of the drug.