A Phase 1-2 Dose-Escalation and Cohort-Expansion Study of Oral Tomivosertib (eFT-508) in Subjects With Hematological Malignancies

Study Overview
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Brief Summary
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This clinical trial is a Phase 1-2, open-label, sequential-group, dose-escalation and cohort-expansion study evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of Tomivosertib (eFT-508). The study will evaluate oral daily administration of Tomivosertib (eFT-508). Treatment and study subject evaluation will be performed in 21-day cycles.

Official Title
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A Phase 1-2 Dose-Escalation and Cohort-Expansion Study of Oral Tomivosertib (eFT-508) in Subjects With Hematological Malignancies

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: Tomivosertib (eFT-508)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Presence of an active hematological malignancy. Presence of measurable disease. Hematological malignancy has been previously treated, has relapsed after or progressed during prior therapy, and has limited potential for benefit from currently available therapy including hematopoietic stem cell transplantation. At least 2 weeks post any treatments/therapies at the time of first dose. Adequate bone marrow function. Adequate hepatic function. Adequate renal function. Normal coagulation panel. Negative antiviral serology. Willingness to use effective contraception. Exclusion Criteria: Central nervous system malignancy Gastrointestinal disease Significant cardiovascular disease Significant ECG abnormalities. Ongoing risk for bleeding due to active peptic ulcer disease, bleeding diathesis or requirement for systemic anticoagulation Ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infections) Pregnancy or breastfeeding. Major surgery within 4 weeks before the start of study therapy. Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids Use of drugs that could prolong the QT interval within 7 days before the start of study therapy. Use of drugs that might pose a risk of a drug-drug interaction within 2-7 days before the start of study therapy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tomivosertib (eFT-508) Escalation Cohort<br>This portion of the study will evaluate the safety and pharmacology of a range of Tomivosertib (eFT-508) doses administered daily in subjects with previously treated lymphomas | Drug: Tomivosertib (eFT-508)<br>* eFT508<br>|
| Experimental: Tomivosertib (eFT-508) Expansion Cohort<br>This portion of the study provides cohort expansion to further explore the safety, pharmacology, and clinical activity of a single dose level of Tomivosertib (eFT-508) monotherapy in subjects with specific previously treated lymphomas | Drug: Tomivosertib (eFT-508)<br>* eFT508<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose and/or Recommended Dose within the tested Tomivosertib (eFT-508) dose range |  | up to one year | 
| Overall Response Rate |  | up to three years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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small molecule inhibitor of protein translation, immunomodulator, phase 1 dose escalation