A Phase I/IIa Open-Label, Dose Escalation and Cohort Expansion Trial of Oral TSR-011 in Patients With Advanced Solid Tumors and Lymphomas
Study Details
Study Description
Brief Summary
TSR-011 is a potent small molecule inhibitor of tyrosine kinases involved in cancer, including:
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Anaplastic lymphoma kinase (ALK)
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The tropomyosin-related kinases TRKA, TRKB, and TRKC
This is a sequential, open-label, non-randomized study with dose escalation in Phase 1, followed by expansion at a recommended phase 2 dose.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Experimental Drug TSR-011 Experimental Drug TSR-011 |
Drug: TSR-011
Number of cycles until progression or unacceptable toxicity develops.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Incidence of Adverse Events (AEs) [Approximately 2 years]
Secondary Outcome Measures
- Area Under the Concentration-Time Curve (AUC) [Day 1: 0-24 hrs after first dose; pre-dose on days 8 & 15; day 29: 0-24 hours]
- Maximum Tolerated Dose (MTD) [28 days after first dose]
Phase 1, during the dose-escalation phase
- Response Rate (RR) [approximately 2 years]
Phase 2
- Dose limiting toxicity (DLT) [28 days after first dose]
Phase 1, during the dose escalation phase
- Progression Free Survival (PFS) [approximately 2 years]
Phase 2
- Recommended Phase 2 Dose (RP2D) [approximately 2 years]
Phase 1
Eligibility Criteria
Criteria
Inclusion Criteria:
- To be considered eligible to participate in this study, all of the following requirements must be met:
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Patients in Phase 1 must have metastatic or locally advanced solid tumors who have failed to respond to standard therapy
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All patients must have confirmation of either ALK positive or TRK positive status.
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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.
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All patients enrolled in this study must have tumor tissue available.
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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).
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Patient must have performance status ≤2 on the ECOG Performance Scale.
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Patient must have an estimated life expectancy of at least 3 months.
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Patients must have adequate organ function.
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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.
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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.
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The patient or his or her legal representative must be able to read, understand, and provide signed informed consent.
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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:
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Patient has leukemia.
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Patient is a pregnant or lactating female.
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Patient has uncontrolled congestive heart failure, angina, or has had a myocardial infarction in the preceding 3 months.
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Ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥2, atrial fibrillation of any grade, or QTc interval >450 msec.
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Patients with risk factors for Torsade de point and patients receiving concomitant medication with QT-prolonging medicines.
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Patient has an uncontrolled concurrent medical condition or disease.
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Patient has undergone bone marrow or stem cell transplantation in the past 6 months.
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Patient has a known hypersensitivity to the components of TSR-011 or the excipients.
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Patient has active or uncontrolled infection.
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Patient has a known psychiatric or substance abuse disorder.
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Patient has active second primary malignancy.
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Patient is observed to have a clinically active central nervous system (CNS) metastases or carcinomatous meningitis.
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Patient has any other severe concurrent disease which, in the judgment of the Investigator, would preclude study participation.
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Patient is known to be HIV positive or who has an AIDS-related illness.
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Patient has a known history of or active (treated or not) Hepatitis B or C.
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Patient has presence of ascites causing significant symptoms.
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A patient must stop taking any prescription, over-the-counter, or herbal remedy known to be an inhibitor or inducer of CYP3A4/5.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Goodyear | Arizona | United States | ||
2 | Scottsdale | Arizona | United States | ||
3 | Los Angeles | California | United States | ||
4 | Nashville | Tennessee | United States | ||
5 | Norfolk | Virginia | United States | ||
6 | Spokane | Washington | United States | ||
7 | Warsaw | Mazowieckie | Poland | ||
8 | Gdansk | Pomorskie | Poland | ||
9 | Olsztyn | Warminsko-Mazurskie | Poland | ||
10 | Poznan | Wielkopolskie | Poland | ||
11 | Madrid | Spain | |||
12 | Santiago de Compostela | Spain | |||
13 | Tainan City | Taiwan | |||
14 | Taipei | Taiwan | |||
15 | London | United Kingdom |
Sponsors and Collaborators
- Tesaro, Inc.
Investigators
- Study Director: Dmitri Bobilev, MD, Tesaro, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PR-20-5006-C