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


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Advanced Malignancies, Carcinoma, Non-Small-Cell Lung, Anaplastic Large Cell Lymphoma, Diffuse Large Cell Lymphoma, Inflammatory Myofibroblastic Tumors

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Trial Information

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


This is the first assessment of AP26113 in patients. The trial will be conducted in 2
parts: an initial dose escalation phase in 30 to 50 patients with advanced malignancies (all
histologies other than leukemia), resistant to available therapies or for whom no standard
or available curative treatments exist, followed by an expansion phase in 4 histologically
and molecularly defined cohorts of patients (20 patients per cohort, approximately 80
patients altogether). The objectives of the dose escalation phase are to determine the
safety, tolerability, pharmacokinetic profile, and recommended phase 2 dose (RP2D) of orally
administered AP26113. The objectives of the expansion phase are to describe the preliminary
anti-tumor activity (overall response rate) of AP26113 in patients with non-small cell lung
cancer (NSCLC) with anaplastic lymphoma kinase (ALK) gene rearrangement or mutated epidermal
growth factor receptor (EGFR), and in patients with any cancers with abnormalities in ALK or
other targets against which AP26113 is active, and to continue to assess safety and
tolerability.

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.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Recommended Phase 2 Dose (RP2D)

Outcome Time Frame:

Day 1 to 28 (Cycle 1)

Safety Issue:

Yes

Authority:

United States: Food and Drug Administration

Study ID:

AP26113-11-101

NCT ID:

NCT01449461

Start Date:

September 2011

Completion Date:

September 2015

Related Keywords:

  • Advanced Malignancies
  • Carcinoma, Non-Small-Cell Lung
  • Anaplastic Large Cell Lymphoma
  • Diffuse Large Cell Lymphoma
  • Inflammatory Myofibroblastic Tumors
  • Advanced Malignancies
  • Carcinoma, Non-Small-Cell Lung
  • Anaplastic Large Cell Lymphoma
  • Diffuse Large Cell Lymphoma
  • Inflammatory Myofibroblastic Tumors
  • Anaplastic Lymphoma Kinase (ALK)
  • Epidermal Growth Factor Receptor (EGFR)
  • Advanced Cancers
  • AP26113
  • Neoplasms
  • Carcinoma
  • Carcinoma, Non-Small-Cell Lung
  • Lymphoma
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Large-Cell, Anaplastic
  • Granuloma, Plasma Cell

Name

Location

The University of Texas MD Anderson Cancer CenterHouston, Texas  77030-4009
Scottsdale Healthcare, Site #134Scottsdale, Arizona  85258
University of California, San Diego: Moores Cancer Center, Site #099San Diego, California  92093
University of Colorado Hospital, Site #015Aurora, Colorado  80045
Yale University, Site #033New Haven, Connecticut  06520
University of Chicago Medical Center, Site #001Chicago, Illinois  60637
Mass General Hospital (MGH), Site #047Boston, Massachusetts  02114
University of Pennsylvania, Site #013Philadelphia, Pennsylvania  19104