A Study of ATG-010 in Combination With ATG-008 in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma

Study Overview
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Brief Summary
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This is an Open label, Phase Ⅰb Study of ATG-010 in Combination With ATG-008 in Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma (RR DLBCL)

Detailed Description
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This is a multi-center, open label, phase 1 study conducted in RR DLBCL patients. The MTD and/or RP2D of study treatment, ATG-010 in combination with ATG-008, will be selected using BOIN design for the dose escalation phase. Additional patients will be enrolled as an expansion cohort after MTD and/or RP2D is determined.

Official Title
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An Open Label, Phase Ⅰb Study of ATG-010 in Combination With ATG-008 in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (RR DLBCL)

Conditions
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Relapsed/Refractory Diffuse Large B-cell Lymphoma

Intervention / Treatment
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* Combination Product: ATG-010 and ATG-008


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years old. ECOG Performance score of ≤2. Estimated life expectancy of >3 months. Previously treated, pathologically confirmed DLBCL Patients must have received at least 2 but no more than 5 previous systemic regimens (for non-DH/TH, non-DE DLBCL and DLBCL not transformed from FL or CLL), or at least 1 but no more than 5 previous systemic regimens (for DH/TH, DE DLBCL, and DLBCL transformed from FL or CLL) for the treatment of their DLBCL. Prior stem cell transplantation is allowed; induction, consolidation, stem cell collection, preparative regimen and transplantation ± maintenance are considered a single line of therapy. Salvage chemoimmunotherapy followed by stem cell transplantation will be considered as 1 line of therapy. Any maintenance therapy will not be counted as a separate line of systemic therapy. Radiation with curative intent for localized DLBCL will not be counted as 1 line of therapy Documented radiographic evidence of progressive DLBCL of the last line (or refractory DLBCL) prior to the first dosing. Exclusion Criteria: Female patients who are pregnant or lactating DLBCL with mucosa-associated lymphoid tissue [MALT] lymphoma, or primary mediastinal (thymic) large B-cell lymphoma (PMBL) Known central nervous system lymphoma or meningeal involvement (for dose expansion phase, patients with stable CNS disease could be considered). Patients eligible for high-dose chemotherapy with autologous stem cell transplantation rescue (the Investigator must provide detailed documentation for ineligibility) Use of any standard or experimental anti-DLBCL therapy (including radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancer therapy) <21 days prior to Cycle 1 Day 1. Autologous stem cell transplant (SCT) <6 months or prior allogeneic SCT, or CAR-T cell infusion <6 months prior to Cycle 1. Major surgery within 4 weeks of the first dose of study treatment.

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 and ATG-008<br>ATG-010 and ATG-008 should be taken 6 hours apart on a PK sampling day | Combination Product: ATG-010 and ATG-008<br>* Patients enrolled will receive consecutive daily treatment at assigned dose level. The starting dose of ATG-010 at the dose escalation phase will be 60 mg QW, which could be escalated to 80 mg QW, 100 mg QW, 60 mg BIW. In case 60 mg QW of ATG-010 with any dose of ATG-008 is NOT tolerable, 40 mg QW ATG-010 could be explored. The starting dose of ATG-008 will be 15 mg QD, which could be escalated to 20 mg QD, with maximum of 30 mg QD. SRC will be consulted before each dose escalation starts.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MTD | Maximum Tolerated Dose | the last patient on study has completed 12 months of follow-up | 
| RP2D | Recommended Phase 2 Dose | the last patient on study has completed 12 months of follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Overall Response Rate | the last patient on study has completed 12 months of follow-up | 
| PFS | Progression Free Survival | the last patient on study has completed 12 months of follow-up | 
| DOR | Duration of Response | the last patient on study has completed 12 months of follow-up | 
| OS | Overall Survival | the last patient on study has completed 12 months of follow-up | 
| TTR | Time To Response | the last patient on study has completed 12 months of follow-up | 
| TTP | Time To Progression | the last patient on study has completed 12 months of follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphoma, Hodgkin's lymphoma , non-Hodgkin's lymphoma