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

Status: Recruiting
Diagnosis: Lung Cancer
NCT ID: NCT01449461 (View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 11-391


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.


Conducting Institutions:
Massachusetts General Hospital

Overall PI:
Alice Shaw, MD, PhD, Massachusetts General Hospital

Site-responsible Investigators:

Massachusetts General Hospital: Cancer Trials Call Center, 877-789-6100

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 at least one (1) prior ALK inhibitor: - Histologically confirmed NSCLC - Tumor tissue available for analysis - ALK rearrangement by FISH - Resistant to at least one (1) prior ALK inhibitor. 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 to 2. - 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 that for cohorts 3 and 4, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy is allowed up to 72 hours prior to initiating AP26113) - Major surgery within 28 days prior to initiating AP26113. - Active metastases in the brain or central nervous system (CNS). - 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 prolong the QT interval. - 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.
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