IPI-504 in NSCLC Patients With ALK Translocations

Inclusion Criteria:

• Patients must have pathologically confirmed diagnosis of Stage IIIb (with malignant pleural or pericardial effusion), Stage IV, or recurrent NSCLC.
• Patients must have demonstrated ALK mutation
• There is no requirement for a minimum or maximum number of prior therapies, however, patients must have refused, be intolerant to or already received at least on standard systemic therapy for lung cancer
• Measureable disease by RECIST criteria. If a patient has received radiation therapy then measurable disease must be outside the radiation field.
• 18 years of age or older
• Life expectancy of at least 3 months
• ECOG performance status of 0-2
• Baseline studies for determining eligibility, except for ALK mutation status, must be completed within 30 days of first study dose.
• CT scan must be completed within 28 days prior to first study dose
• Women of child-bearing potential (WBCP) defined as a sexually mature woman who has not undergone a hysterectomy or who has not been naturally post-menopausal for at least 24 consecutive months must have a negative serum or urine pregnancy test within 2 weeks of first study dose
• All WCBP and all sexually active male patients must agree to use adequate methods of birth control throughout the study

Exclusion Criteria:

• Treatment for NSCLC with any approved or investigational product within 2 weeks of Cycle 1, Dose 1 for any small molecule therapy; within 4 weeks of Cycle 1, Dose 1 for any biologic or any conventional chemotherapy.
• Concurrent radiation therapy is not permitted
• Use of a medication or food that is clinically relevant CYP3A inhibitor or inducer within 2 weeks prior to Cycle 1, Dose 1
• Laboratory values as outlined in the protocol
• Baseline QT corrected using Fridericia's correction method (QTcf) > 470ms. Patients with left bundle branch block are eligible regardless of QTcf, as long as serum troponin is normal or undetectable
• Presence of active infection or systemic use of antibiotics within 72 hours of treatment
• Significant co-morbid condition or disease which in the judgment of the investigator would place the patient at undue risk or interfere with the study
• Women who are pregnant or lactating
• Previous treatment with 17-AAG, DMAG, or other known Hsp90 inhibitor
• Sinus bradycardia secondary to intrinsic conduction system disease. Patients with sinus bradycardia secondary to pharmacologic treatment may enroll if withdrawal of the treatment results in normalization of the resting heart rate to within normal limits
• Active keratitis or keratoconjunctivitis
• Alkaline phosphatase > 1.5 x ULN. Patients with bone metastases and an alkaline phosphatase level > 1/5 x ULN and less than or equal to 3 x ULN are eligible if they meet the criteria outlined in the protocol
• Prothrombin time (PT) and partial thromboplastin time (PTT) > 1.5 x ULN unless the patient is receiving warfarin. If the patient is receiving warfarin, the international normalized ratio must be within therapeutic range
• Patients with clinically active brain metastasis or an uncontrolled seizure disorder, ongoing spinal cord compression, or carcinomatous meningitis. Patients with clinically stable brain metastasis are eligible.
• Patients with prior hepatic resection or hepatic-directed therapy