A Study of Evaluating the Safety and Efficacy of ATG-010 in Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Study Overview
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Brief Summary
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This is an open-label, single arm, and registered study of ATG-010 in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma.

Detailed Description
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This is an open-label, single arm, and registered study. About 60 patients with relapsed/refractory DLBCL plan to be enrolled in about 10 study sites of the study. It is planned that at least 50% ( 30 patients) will have the GCB subtype of DLBCL. Enrolled patients will be treated with a fixed dose, 60 mg of ATG-010, orally, twice weekly, each 4 week (28-day) a cycle. Patients should remain on the study treatment of ATG-010, until either PD or occurrence of unacceptable toxicity.

Official Title
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An Open-label and Single Arm Study of ATG-010 in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Conditions
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Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Intervention / Treatment
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* Drug: ATG-010 60 mg, orally, twice weekly, each 4 week (28-day) a cycle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient must provide informed consent form (ICF) prior to the first screening procedure. Age ≥18 years. ECOG performance status of ≤ 2. Patients should have estimated life expectancy of >3 months at study entry. Previously treated, pathologically confirmed de novo DLBCL, or DLBCL transformed from previously diagnosed indolent lymphoma (e.g., follicular lymphoma). Patients must have received at least 2 but no more than 5 previous systemic regimens for the treatment of their de novo or transformed DLBCL. Documented clinical or radiographic evidence of progressive DLBCL prior to dosing. Patients must have measurable disease per the revised criteria for response assessment of lymphoma (Cheson, 2014). Patients must not be eligible for high-dose chemotherapy with autologous stem cell transplantation rescue. Exclusion Criteria: Patients who are pregnant or lactating. DLBCL with mucosa-associated lymphoid tissue (MALT) lymphoma, composite lymphoma (Hodgkin's lymphoma +NHL), or DLBCL transformed from diseases other than indolent NHL or Richter's. Primary mediastinal (thymic) large B-cell lymphoma. Known central nervous system lymphoma or meningeal involvement. Patients whose most recent systemic anticancer therapy include radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancer therapy other than glucocorticoids < 6 weeks prior to first dose of study drug. Patients who have not recovered to Grade ≤ 1 clinically significant adverse events, or to their baseline, from their most recent systemic anti-DLBCL therapy. Patients with active graft-versus-host disease after allogeneic stem cell transplantation. At least 4 months must have elapsed since completion of allogeneic stem cell transplantation. Major surgery within 2 weeks of first dose of study treatment of ATG-010. Any life-threatening illness, medical condition or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety. Active hepatitis B virus or hepatitis C virus infection. Known human immunodeficiency virus infection.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ATG-010<br>Enrolled patients will be treated with a fixed dose, 60 mg of ATG-010. | Drug: ATG-010 60 mg, orally, twice weekly, each 4 week (28-day) a cycle<br>* Enrolled patients will be treated with a fixed dose, 60 mg of ATG-010, orally, twice weekly, each 4 week (28-day) a cycle.<br>* Other names: Selinexor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Percentage of subjects with PR, or CR | 6 months after the last subject was enrolled | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DOR | Duration of time from first occurrence of CR or PR until the first date that disease progression is objectively documented | 6 months after the last subject was enrolled | 
| DCR | Proportion of patients who achieve CR, PR, or SD for a minimum of 4 weeks, following the first dose of study drug (i.e., CR+PR+SD) | 6 months after the last subject was enrolled | 
| OS | Duration of time from the first dose of study drug until death due to any cause | 6 months after the last subject was enrolled | 
| PFS | Duration of time from the first dose of study drug until progression or death due to any cause | 6 months after the last subject was enrolled |