A Phase 1/2 Study of the Oral ALK/EGFR Inhibitor AP26113


Anus | Bladder | Bones and Joints | Brain and Nervous System | Breast - Female | Breast - Male | Cervix Uteri | Colon | Corpus Uteri | Esophagus | Eye and Orbit | Hodgkin's Lymphoma | Ill-Defined Sites | Kidney | Larynx | Lip, Oral Cavity and Pharynx | Liver | Lung | Lung Cancer | Melanoma, skin | Multiple Myeloma | Non-Hodgkin's Lymphoma | Other Digestive Organ | Other Endocrine System | Other Female Genital | Other Male Genital | Other Urinary | Ovary | Pancreas | Prostate | Rectum | Small Intestine | Soft Tissue | Stomach | Thyroid

Trial Phase

Phase I-II

Trial Purpose and Description

Trial Purpose

The purpose of this study is 2-fold: initially, in the dose escalation phase, the goal is to determine the safety profile of orally administered AP26113, including: the maximum tolerated dose (MTD), dose limiting toxicities (DLTs), recommended phase 2 dose (RP2D), and pharmacokinetic (PK) profile. Then, once the RP2D is established, an expansion phase will assess the preliminary anti-tumor activity of AP26113, both in non-small cell lung cancer (NSCLC) with ALK gene rearrangement or mutated EGFR, and in other cancers with abnormal targets against which AP26113 is active. Approximately 110 to 130 patients will be enrolled.

Participation Guidelines

18 Years and older

Eligibility 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

- 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

- 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

- 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.

Ariad Pharmaceuticals Inc.
Last Updated:
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