SHS_492405 PARM CARI 17177

A Phase 1/2 Study of the Safety, Pharmacokinetics, and Anti-Tumor Activity of the Oral EGFR/HER2 Inhibitor AP32788 in Non-Small Cell Lung Cancer

General Inclusion Criteria (all dose escalation and expansion cohorts):

• Have histologically or cytologically confirmed locally advanced (and not a candidate for definitive therapy) or metastatic NSCLC (Stage IIIB or IV).

• Must have measurable disease by RECIST v1.1

• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.

• Minimum life expectancy of 3 months or more.

• Adequate renal and hepatic function as defined by the following criteria:

• Total serum bilirubin ≤2 × upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN (or ≤5 × ULN if liver function abnormalities are due to underlying malignancy); Estimated creatinine clearance ≥ 60 mL/min (calculated by using the Cockcroft-Gault equation); and Serum albumin ≥2 g/dL.

• Adequate bone marrow function as defined by the following criteria:

• Absolute neutrophil count (ANC) ≥1.5 × 109/L; f. Platelet count ≥75 × 109/L; and g. Hemoglobin ≥9.0 g/dL.

• Normal QT interval on screening electrocardiogram (ECG), defined as QT interval corrected (Fridericia) (QTcF) of ≤450 ms in males or ≤470 ms in females.

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

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

Exclusion Criteria:

• Received systemic anticancer therapy (including cytotoxic chemotherapy, investigational agent, antineoplastic monoclonal antibodies, or immunotherapy) ≤14 days prior to first dose of AP32788 (except for reversible EGFR TKIs [ie, erlotinib or gefitinib], which are allowed up to 7 days prior to the first dose of AP32788).

• Have been diagnosed with another primary malignancy other than NSCLC except for adequately treated non-adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic prostate cancer; or patients with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy.

• Received a potent CYP3A inhibitor within 7 days or potent CYP3A inducer within 5 weeks prior to first dose of AP32788.

• Have undergone major surgery within 28 days prior to first dose of AP32788. Minor surgical procedures, such as catheter placement or minimally invasive biopsy, are allowed.

• Have brain metastases that are neurologically unstable or require an increasing dose of corticosteroids.

• Have symptomatic leptomeningeal carcinomatosis or spinal cord compression. Patients with asymptomatic leptomeningeal disease and no evidence of spinal cord compression are allowed.

• Have significant, uncontrolled, or active cardiovascular disease

• History of clinically significant (as determined by the treating physician) atrial arrhythmia; Any history of ventricular arrhythmia; or Cerebrovascular accident or transient ischemic attack within 6 months prior to first dose.

• Have a known history of uncontrolled hypertension.

• Have prolonged QTcF interval, or being treated with medications known to be associated with the development of Torsades de Pointes.

• Have an ongoing or active infection, including but not limited to, the requirement for intravenous (IV) antibiotics, or a known history of human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). Testing is not required in the absence of history.

• Currently have or have a history of interstitial lung disease, drug-related pneumonitis, or radiation pneumonitis that required steroid treatment.

• Are pregnant or breastfeeding.
Phase I/II
Min Sung Park, M.D.
ARIAD Pharmaceuticals, Inc
Mai Berenfeld
  • Swedish Medical Center