A Phase I/IIa Open-Label, Dose Escalation and Cohort Expansion Trial of Oral TSR-011 in Patients With Advanced Solid Tumors and Lymphomas

Inclusion criteria

• To be considered eligible to participate in this study, all of the following requirements must be met:

• Patients in Phase 1 must have metastatic or locally advanced solid tumors who have failed to respond to standard therapy
• All patients must have confirmation of either ALK positive or TRK positive status.
• Patients in Phase 1 will not be required to have measurable disease. All patients in Phase 2a will be required to have measurable disease by RECIST.
• All patients enrolled in this study must have tumor tissue available.
• Patient (male or female) must be ≥ 18 years of age (except where age of majority is 16 years in a particular country, such as the United Kingdom).
• Patient must have performance status ≤2 on the ECOG Performance Scale.
• Patient must have an estimated life expectancy of at least 3 months.
• Patients must have adequate organ function.
• For patients previously treated with myelosuppressive therapy, at least 3 weeks must have elapsed and toxicity must have recovered to grade 1 or baseline. Non-myelosuppressive therapy patients must have recovered from all treatment-related toxicities. Fourteen days must have elapsed since palliative radiation for bone metastasis.
• Female patients of childbearing potential must have a negative serum pregnancy test and use adequate birth control for the duration of study participation and for 3 months after the last dose of study drug.
• The patient or his or her legal representative must be able to read, understand, and provide signed informed consent.
• Patient is able to understand the study procedures and agrees to participate in the study by giving written informed consent.

Exclusion criteria

• Patients will not be deemed eligible for entry into this study if any of the following criteria are met:

• Patient has leukemia.
• Patient is a pregnant or lactating female.
• Patient has uncontrolled congestive heart failure, angina, or has had a myocardial infarction in the preceding 3 months.
• Ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥2, atrial fibrillation of any grade, or QTc interval >450 msec.
• Patients with risk factors for Torsade de point and patients receiving concomitant medication with QT-prolonging medicines.
• Patient has an uncontrolled concurrent medical condition or disease.
• Patient has undergone bone marrow or stem cell transplantation in the past 6 months.
• Patient has a known hypersensitivity to the components of TSR-011 or the excipients.
• Patient has active or uncontrolled infection.
• Patient has a known psychiatric or substance abuse disorder.
• Patient has active second primary malignancy.
• Patient is observed to have a clinically active central nervous system (CNS) metastases or carcinomatous meningitis.
• Patient has any other severe concurrent disease which, in the judgment of the Investigator, would preclude study participation.
• Patient is known to be HIV positive or who has an AIDS-related illness.
• Patient has a known history of or active (treated or not) Hepatitis B or C.
• Patient has presence of ascites causing significant symptoms.
• A patient must stop taking any prescription, over-the-counter, or herbal remedy known to be an inhibitor or inducer of CYP3A4/5.